Diabetic peripheral neuropathy (DPN) is the most common chronic complication of diabetes and presently has no long term treatment. The long-term goal of this project is to develop therapeutic stem cell based treatments for people experiencing DPN and other debilitating neuropathies. The overall objective of this application is to characterize our novel stem cell population and evaluate the safety of transplantation and efficacy of treatment in an animal model of diabetes with associated DPN. The central hypothesis is that transplantation of insulin-like growth factor I (IGF-I) producing periodontal ligament stem cells (PDLSC) into an animal model of diabetes will minimize the painful effects of DPN. The rationale for the proposed research is that a long term treatment for DPN and other neuropathic diseases may be achieved through the implantation of neurotrophic-releasing stem cells, creating a micro-environment that will arrest or reduce the effects of this debilitating condition. The specific aims of this project are: Aim 1: Characterize neurotrophic secretion levels of novel PDLSC to determine dosing requirements for animal studies. Aim 2: Evaluate the effects of transplanting neurogenic and non-neurogenic committed PDLSC into an animal model of diabetes with associated DPN. The primary approach is to develop neuro-induction protocols and characterize our novel stem cell population, and then transplant these cells into an animal model of diabetes with associated DPN and evaluate the effects of transplantation on pain evoked behaviors. The contribution of this project will be significant because it is the initial stp in a continuum of research towards a long-term stem-cell based treatment designed specifically to address DPN.